Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality both in the United States and worldwide. Based on the 2014 Heart Disease and Stroke Update by the American Heart Association (AHA), 83.6 million American adults have at least one type of CVD (>1 in 3 prevalence). Of these adults, 15.4 million suffer from coronary heart disease (CHD), with the following breakdown: myocardial infarction (MI): 7.6 million and angina pectoris (AP): 7.8 million. It is estimated that by 2030, 43.9% of the US population will have some form of CVD.
The underlying cause of CVD is atherosclerotic coronary artery disease (ASCAD), which begins with the development of an atherosclerotic plaque in the coronary arterial vasculature. Atherosclerosis is of unquestionable importance, in terms of human health and societal cost. It is responsible for coronary artery disease (CAD) and cerebro-vascular disease, both of which are leading causes of morbidity and mortality worldwide. Atherosclerosis is also responsible for peripheral arterial disease, a leading medical cause of limb-loss.
The development and progression of atherosclerotic CAD follows two distinct paths that may lead from one to another, and lead to two distinct clinical syndromes. One of the two broad clinical syndromes is “exertional angina”, also called “stable angina” or “stable CAD.” In this context, progressively growing atherosclerotic plaque leads to progressively worsening coronary arterial luminal stenosis, or narrowing, that starts to impede blood flow to the myocardium (heart muscle). When luminal stenosis, or narrowing, reaches a critical limit, approximately 70% diameter stenosis, there is significant pressure drop over the stenosis, and myocardial perfusion (blood flow to the heart muscle) is compromised, especially during periods of increased myocardial oxygen demand, such as during exertion or emotional states. This myocardial oxygen “supply-demand mismatch” leads to myocardial ischemia, when blood flow to the heart muscle can no longer keep up with demand. It is myocardial ischemia itself that triggers pain receptors in the heart, leading to the clinical symptoms of “angina pectoris”, or chest pain. While this process typically causes chest pain during exertion or emotional states, this typically does not lead to acute coronary syndromes, such as sudden cardiac death (SCD), myocardial infarction (MI; heart attack) or unstable angina (UA). Typical treatment options include medical interventions to slow the heart rate with beta blockers or calcium channel blockers, and to improve blood flow with drugs like nitrates. Typical interventional approaches are aimed at relieving the stenosis, by either percutaneously placing a stent inside the stenosis (percutaneous coronary intervention; PCI) to open the narrowing, or to bypass the stenotic (narrowed) segment using arterial or venous grafts during coronary artery bypass grafting (CABG) surgery. As pointed out above, the root cause of this pathophysiology and clinical course of “exertional angina” is coronary arterial atherosclerosis, or atherosclerotic CAD.
The second broad path in pathophysiology with a corresponding clinical picture is referred to as “acute coronary syndromes” (ACS), which encompasses sudden cardiac death (SCD), myocardial infarction (MI) and unstable angina (UA). In this context, the atherosclerotic plaque (the root cause) in the coronary artery can get disrupted either through rupture, or erosion. When a coronary atherosclerotic plaque gets disrupted, this triggers the formation of a thrombus (clot) over the disrupted region, which may partially or completely occlude the entire coronary artery, leading to abrupt cutoff of blood supply to the myocardium (acute myocardial ischemia). This pathophysiology may manifest in sudden cardiac death (SCD), myocardial infarction (MI), or resting angina. Typical treatment options are commonly interventional options, where the acutely disrupted plaque is covered up with a stent during an invasive procedure. Just as in the case of “exertional angina”, the root cause of acute coronary syndromes is atherosclerotic plaque in the coronary arterial vasculature.
Accordingly, the initiation and progression of atherosclerotic plaques are the root cause of the clinical manifestations of atherosclerotic CAD and CHD. Thus, there remains a need for improved diagnostic methods for detecting an atherosclerotic plaque and for diagnosing atherosclerotic CAD.